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They play a crucial role in shaping cellular identity and driving the progression of various diseases, including cancer. SEs exhibit significant heterogeneity across different cell types and cancer subtypes. Analysis of SE landscapes can recapitulate existing classification systems and unveil novel SE-driven epigenetic subtypes. In this review, we summarized the latest advancements in cancer subtype identification based on SE-related characteristics, outlined the typical analytical workflows adopted in such studies, and explored the biological and clinical significance of SE-driven subtypes. Furthermore, we discussed the field\u2019s key challenges and emerging technologies to highlight future research directions. SE analysis provides a robust framework for dissecting cancer heterogeneity. This approach offers novel epigenetic perspectives and support for the realization of personalized medicine.<\/jats:p>","DOI":"10.1093\/bib\/bbaf596","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T15:42:26Z","timestamp":1762789346000},"source":"Crossref","is-referenced-by-count":2,"title":["Decoding cancer heterogeneity through super-enhancer landscapes: from subtype discovery to therapeutic opportunity"],"prefix":"10.1093","volume":"26","author":[{"given":"Shuyang","family":"Cai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University , No. 2 SEU Road, Nanjing, Jiangsu 211189 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenchang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University , No. 2 SEU Road, Nanjing, Jiangsu 211189 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-7775","authenticated-orcid":false,"given":"Xiao","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University , No. 2 SEU Road, Nanjing, Jiangsu 211189 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5570-6145","authenticated-orcid":false,"given":"Hao","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University , No. 2 SEU Road, Nanjing, Jiangsu 211189 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"2025111010422221800_ref1","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/0092-8674(80)90358-X","article-title":"High efficiency transformation by direct microinjection of DNA into cultured mammalian cells","volume":"22","author":"Capecchi","year":"1980","journal-title":"Cell"},{"key":"2025111010422221800_ref2","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/0092-8674(89)90110-4","article-title":"An enhancer stimulates transcription in trans when attached to the promoter via a protein bridge","volume":"58","author":"M\u00fceller-Storm","year":"1989","journal-title":"Cell"},{"key":"2025111010422221800_ref3","doi-asserted-by":"publisher","first-page":"5667","DOI":"10.1242\/dev.00157","article-title":"The drosophila pox neuro gene: control of male courtship behavior and fertility as revealed by a complete dissection of all enhancers","volume":"129","author":"Boll","year":"2002","journal-title":"Dev Camb Engl"},{"key":"2025111010422221800_ref4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nature12753","article-title":"Topology of mammalian developmental enhancers and their regulatory landscapes","volume":"502","author":"Laat","year":"2013","journal-title":"Nature"},{"key":"2025111010422221800_ref5","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.cell.2013.03.035","article-title":"Master transcription factors and mediator establish super-enhancers at key cell identity genes","volume":"153","author":"Whyte","year":"2013","journal-title":"Cell"},{"key":"2025111010422221800_ref6","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/ng.3167","article-title":"What are super-enhancers?","volume":"47","author":"Pott","year":"2015","journal-title":"Nat Genet"},{"key":"2025111010422221800_ref7","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1126\/science.aaa3247","article-title":"Cancer. 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